Treatment-Induced Decline of Human Immunodeficiency Virus-1 p24 and HIV-1 RNA in Lymphoid Tissue of Patients with Early Human Immunodeficiency Virus-1 Infection

Abstract

We report detailed quantitative analysis of human immunodeficiency virus-1 (HIV-1) p24 and HIV-1 RNA in tonsil biopsies from 13 patients with early, asymptomatic HIV infection before and during combination antiretroviral therapy. Using fluorescent microscopy in conjunction with reverse transcriptase-polymerase chain reaction of frozen tissue sections, we show that plasma and tissue viral loads decreased by approximately 3 logs during the 1-year treatment period, with good correlation between the HIV-1 p24 and HIV-1 RNA response in tissue. The decrease of tissue viral load was delayed compared to plasma viral load, possibly explained by the observation that the amount of follicular dendritic cell-associated virus correlated best with the area under the curve of plasma HIV-1 RNA throughout the last 12 weeks. Before and during treatment, the relative proportions of HIV-1 on follicular dendritic cells and within mononuclear cells remained constant, suggesting similar decay characteristics in these two lymphoid tissue compartments. However, viral p24 or RNA remained almost always detectable in tissue despite full suppression of HIV-1 RNA in plasma, and increased even after short-term rebounds in plasma viral load. Thus, full and sustained suppression of viral replication was required to efficiently decrease viral load in lymphoid tissue, but complete abolition of residual viral replication was not achieved.